This invention is directed to a method and composition for the alteration of the adhesiveness of pressure-sensitive adhesives used in transdermal delivery devices. Patch-type devices are well known for the transdermal administration of pharmaceutical agents as well as cosmetics, emollients and other skin treating agents. These patch-type devices are used for the administration of numerous classes of drugs or skin treating products. This invention is directed to a composition and method whereby the adhesiveness of the associated pressure sensitive adhesive of a transdermal delivery device is altered, rendering the device inherently less damaging to the skin of the patient than prior art patches.
Matrix-type transdermal delivery devices are designed to adhere to the skin for a period of time sufficient to allow administration of an active permeant or skin treating agent. Unfortunately, the adhesives in common use in transdermal devices often adhere too strongly to the area of application resulting in skin irritation or peeling of the skin layer when the patch is removed. The strength with which the device adheres to the skin is determined, to some extent, by the chemicals used and the molecular weight properties of the pressure sensitive adhesive.
The strength with which the device adheres to the skin is often touted as a beneficial attribute. This perspective is especially true where the device displays an ability to adhere strongly to the skin for extended periods of time. However, this adhesion tenacity is counter-productive if the removal of the device causes damage to the tissue to which it had been adhered. This is especially true where the device is a transdermal device which is adhered to sensitive tissue. This sensitive tissue may be, for example, an infected area in need of treatment, a preferred skin site for the administration of a type of drug to be transdermally delivered or a skin area which is inherently sensitive.
An infected skin site could be treated by a transdermal delivery system to administer an useful pharmaceutical agent directly to the infected tissue. Such treatment may be to compromised tissue to which an adhesive device will be bound and removal of the transdermal device could cause additional damage.
A preferred site of application is largely determined by the pharmaceutical agent, cosmetic, emollient, etc., that is administered. For example, a drug designed to alleviate an erectile dysfunction condition might need to be applied to the penis or nearby tissue. The application of an adhesive device to such sensitive tissue creates the ability of the adhesive to be removed easily and painlessly.
Moreover, transdermal treatment with emollients, cosmetics or bioactive agents has been found to be useful for the treatment of wrinkles. The treatment of wrinkles involves the adhesion of a transdermal device to a site, such as around the eye, for a short duration, such as overnight. Removal of adhesive patches from facial tissues and particularly around the eye is painful and can be emotionally traumatic. Following such treatment it would be useful for the device to be removed without causing additional dermal trauma or visible irritation.
Regardless of the application site, it would be desirous to have an adhesive combination which adheres effectively, but less strongly, than adhesives now known. It would be further desirous to have an adhesive for use in transdermal administration devices which facilitated both the transdermal delivery of the pharmaceutical or other bioactive agent and the facile removal of the device from the application site without the associated irritation, pain and trauma often caused by removal of pressure-sensitive adhesives.
One shortcoming of patch-type devices, particularly matrix devices in which the active agent is intimately dissolved or dispersed in the adhesive, involves the irritation caused to the skin secondary to removal of the adhesive device. The damage caused by strong adherence to the skin often involves substantial desquamation and ulceration upon removal of the device. Additionally, such devices cause substantial irritation of the adhered tissue during administration of the drug or other agent.
It would therefore be desirable to provide a transdermal device where the adhesive composition did not cause these undesirable irritations, desquamation and ulcerations.
It is therefore an object of the invention to provide a pressure-sensitive adhesive transdermal delivery device which upon removal following use, does not result in irritation, desquamation or ulceration of the treatment site.
It is another object of the invention to provide a pressure-sensitive adhesive transdermal delivery device which minimizes the damage caused to tissue secondary to the removal of the adhesive device.
It is still a further object of the invention to regulate the adhesive strength of a pressure sensitive adhesive patch.
These and other objects of the invention are accomplished through the incorporation of an adhesion-adjusting member, such as a polydiorganosiloxane polymer, intimately admixed with the pressure-sensitive adhesive portion of a matrix-type transdermal delivery device system. It has been discovered that the inclusion of a polydiorganosiloxane polymer into the adhesive portion of a pressure-sensitive adhesive device decreases the strength with which the adhesive adheres to the skin. Furthermore the intimate admixture of a suitable amount of a polydiorganosiloxane polymer member with the adhesive of a matrix-type pressure-sensitive adhesive device provides a device which is designed for short duration applications, such as overnight. In practice, the use of a polydiorganosiloxane polymer member as part of a pressure-sensitive adhesive formulation minimizes the damage caused by the adhesive secondary to the removal of the previously adhered device.
Polydiorganosiloxanes as a class may be utilized as more fully described below. Of that class the polydimethylsiloxanes are particularly preferred and are specifically exemplified. Polydimethylsiloxane polymers and copolymers are also known by the generic name dimethicone. These terms will be used interchangeably throughout this description.
One preferred embodiment is directed to the inclusion of a polydiorganosiloxane polymer into an adhesive formulation which is part of a pressure-sensitive matrix-type device for the treatment of wrinkles. In this matrix patch device the objective is to adhere the device to the skin area to be treated for an effective yet limited time. For example, this area might typically be the skin area around the eye where wrinkles traditionally develop incident to the aging process. After a desired period of time the transdermal device is removed by peeling the adhesive from the skin.
Also, as a result of transdermal administration, the treated skin is sensitive and more prone to irritation or damage. The removal of a patch, where the adhesive portion has been advantageously formulated using the siloxane polymer to adhere less strongly than pressure sensitive adhesives alone, is facile and painless. Where the pressure sensitive adhesives conventionally used in the art would damage and irritate the skin upon their removal, the modulated adhesive composition of this invention is easily removed without discomfort or damage to the underlying skin.
The following definitions will be useful in describing the invention and will eliminate the need for repetitive explanations.
By xe2x80x9ctransdermalxe2x80x9d is meant transdermal or percutaneous administration of an active permeant for delivery through the skin for translocation or systemic delivery. Also, this term includes the application of a skin-treating composition directly to the skin area to be treated. To the extent that the invention can be utilized in the treatment of mucosal tissues they are also included in the term xe2x80x9ctransdermal.xe2x80x9d Hence the terms xe2x80x9cskin,xe2x80x9d xe2x80x9cderma,xe2x80x9d xe2x80x9cepidermis,xe2x80x9d xe2x80x9cmucosa,xe2x80x9d and the like shall also be used interchangeably unless specifically stated otherwise.
By the term xe2x80x9cmatrix,xe2x80x9d xe2x80x9cmatrix patchxe2x80x9d or xe2x80x9cmatrix systemxe2x80x9d is meant the essential permeant or skin-treating components combined in a biocompatible pressure-sensitive adhesive which may or may not also contain other ingredients such as enhancers, anti-irritants, etc. A matrix system is usually an occlusive adhesive patch having an impermeable film backing and, before transdermal application, a release liner on the surface of the adhesive opposite the film backing.
By xe2x80x9cpressure sensitive adhesivexe2x80x9d is meant any biocompatible adhesive that can be used to secure a transdermal device to the skin surface. Representative of such pressure-sensitive adhesives are acrylic copolymers, rubber-based adhesives, ethylene vinyl acetate copolymers, latex polymers and waterborn acrylic copolymers. However, any other suitable pressure-sensitive adhesives may also be used which are compatible with polydiorganopolysiloxane polymer and the skin treating agents as utilized.
By xe2x80x9cchemical agent,xe2x80x9d xe2x80x9cdrug,xe2x80x9d xe2x80x9cpermeant,xe2x80x9d xe2x80x9cskin treating agentxe2x80x9d and the like is meant any biotreating agent that can be delivered transdermally for any purpose. The agent may be selected from the group consisting of drugs, cosmetics, emollients, or other skin treating components. In some instances a chemical agent may be considered as belonging to more than one of the listed groups. For example, vitamins A and E or derivatives thereof may be combined with moisturizing agents, skin collagen synthesis promoting agents and exfoliating agents and the like as an emollient composition for the treatment of wrinkles but could also be considered as a cosmetic.
By xe2x80x9cpolydiorganosiloxane polymerxe2x80x9d is meant a silicone fluid polymer having repeat units of the formula R2SiO2/2 siloxy units where R is a hydrocarbon or substituted hydrocarbon having from about 1 to 20 carbons atoms and is represented by the formula:
(R)3Sixe2x80x94Oxe2x80x94[(R)2Sixe2x80x94Oxe2x80x94]nSi(R)3
where R can be a hydrocarbon or substituted hydrocarbon of 1 to about 20 carbon atoms and can be selected from the group consisting of alkyl, aryl, cycloalkyl and the like which may be substituted to contain halogen, amino, hydroxy, ether or other similar functionalities. The integer xe2x80x9cnxe2x80x9d is sufficient to cause the silicone fluid to have a viscosity of between about 20 and 25,000 centistokes. Preferably the viscosity will be between about 20 and 12,500 centistokes.
Polydiorganosiloxane polymer fluids may be generally classified as unmodified silicones, linear and cyclic volatile silicones, alkyl/alkoxy modified silicones, phenyl modified silicones, aminofunctionalized silicones, polyglucoside silicones and polyether functionalized silicones.
Within the various classes, the polydiorganosiloxane polymer fluids are represented by proprietary tradenames including a number which is generally, but not always, indicative of viscosity.
Representative proprietary polydiorganosiloxane follow.
Exemplary of unmodified silicone fluid polymers are Dimethicone and Dimethiconol available as SP 96(copyright)(20, 50-1000), Visasil(copyright)(5M-100M) and SF18(350) from Costec Inc. (Palatine, Ill.), Dow Corning(copyright) 200 and 225 fluids from Dow Corning Corporation (Midland, Mich.), DM 100-1000, AK 5-1MM, X-345 and F-1006 from Wacker Silicones Corporation (Adrian, Mich.) and Sentry Dimethicone NF from Whitco Corporation (Greenwich, Conn.).
Representative of linear and cyclic volatile silicones are Cyclomethicone ( greater than 4) available as SF 1173, SF 1202 and SF 1204 from Costec Inc., Dow Corning(copyright) 244, 145, 344 and 345 fluids from Dow Corning Corporation and CM 040 from Wacker Silicone Corporation; Dimethicone SF96(copyright) (5) from Costec Inc. and DM 1 plus from Wacker Silicones Corporation; and Hexamethyldisiloxane available as DM 0.65 from Wacker Silicones Corporation.
Typical of alkyl/alkoxy modified silicones include lauryl dimethicone available as Dow Corning(copyright) Q2-5200 from Dow Corning Corp, LDM 3107VP from Wacker Silicones Corp.; Cetyl dimethicone available as Dow Corning(copyright) 2502 from Dow Corning Corp. and DMC 3071 from Wacker Silicones Corp.; Stearyl dimethicone available as SF1632 from Costec, Inc., Dow Corning(copyright) 2504 from Dow Coming Corp., and E32 from Wacker Silicones Corporation.
Illustrative of phenyl modified silicones are Phenyltrimeticone which as available as SF 1550 from Costec Inc., Dow Corning(copyright) 556 fluid from Dow Corning Corporation and PDM 20, 100, 1000 from Wacker Silicones Corporation.
Aminofunctionalized silicones may be represented by Amodimethicone available as SM2658 from Costec, Inc., Dow Corning(copyright) 929 and 939 from Dow Corning Corp. and L650, 652 and ADM 6057E from Wacker Silicones Corporation; Trimethylsilylamodimethicone available as SF1708-D1, SM2101 and SM2115-D2 from Costec, Inc. Dow Corning(copyright) Q2-7224 and Q2-8220 from Dow Coming Corp. and L653, 655, 656 and ADM 3047E from Wacker Silicones Corporation.
Indicative of the class of silicone polyglucosides is Octyl Dimethicone Ethoxy Glucoside (SPG 128) from Wacker Silicones Corporation.
Polyether functionalized silicones are typified by Dimethicone Copolyol available as SF 1188 from Costec, Inc. Dow Coming(copyright) 2501, 3225C, Q2-5324 and Q2-5434 from Down Corning Corp. and DMC 6032 and Cetyl Dimethicone Copolyol available as CMC 3071 from Wacker Silicones Corporation.
The above listings are representative and any polydiorganosiloxane polymer fluid functional for use in adjusting the adhesive properties of a pressure sensitive adhesive may be utilized.
With reference to the above formula, preferably R is methyl and the diorganopolysiloxane is a dimethylpolysiloxane polymer generically known as dimethicone. Therefore the terms xe2x80x9cpolydimethylsiloxanexe2x80x9d and xe2x80x9cdimethiconexe2x80x9d are used interchangeably and refer to the preferred diorganopolysiloxane polymer. Various grades or weights of dimethicone may be referred to in the examples under the trade name Dimethicone xe2x80x9cXXXxe2x80x9d where xe2x80x9cXXXxe2x80x9d is indicative commercially of the viscosity of the polysiloxane polymer.
The siloxane polymer fluid content or concentration to be combined in the pressure-sensitive adhesive may vary over a wide range as long as it effectively regulates or controls the degree of tackiness such that the adhesive retains the transdernal device on the skin of a subject for the desired period of time and yet allows for the efficient removal of the device with no or minimal skin irritation or damage. Generally speaking, the siloxane polymer content may vary between about 0.1 and 20% by weight of the entire pressure-sensitive adhesive layer and will preferably be between about 0.1 and 10% by weight. In other words, where bioactive permeants, skin treating products, anti irritants and other additives are combined in the pressure-sensitive adhesive, the siloxane polymer content will be 0.1 to 20% and preferably 0.1 to 10% by weight of the entire pressure-sensitive adhesive/siloxane polymer/other ingredients combination.